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The human Metapneumovirus (HMPV) has been discovered by von den Hoogen et al. in 2001 and seems to play an important role as etiologic agent in childhood respiratory tract infections in particular involving infants after the 6th month of life and toddlers. Duly considering the hitherto published studies and retrospective analysis of two HMPV seasons (2002-2004) at our institution this review focuses on children, who had to be hospitalized due to HMPV infection. The analysis confirmed, that among those patients there is a high proportion of children with pre-existing risk factors for a complicated clinical course, a high proportion of children with bronchiolitis or pneumonia and a relevant proportion of children with HMPV related apnoeas, most prevalent in the prematurely born. Although the first HMPV infection takes place somewhat later in infancy, the data do not show that HMPV infection is in general milder than RSV infection in hospitalized children. Clinical symptoms and radiological signs do not permit tentative conclusions on the causative agent. This underlines the necessity of specific diagnostic efforts (in case of HMPV with PCR). HMPV may cause lobar or segmental pneumonias difficult to distinguish from bacterial lower respiratory tract infection. Children admitted to the hospital with an acute exacerbation of asthma bronchiale or cystic fibrosis should not only be tested for RSV but also for HMPV. Prospective studies investigating specific therapeutic interventions or describing the impact and prevention of nosocomial HMPV in fection are awaited for. There has been one report of a meningoencephalitis possibly related to HMPV. Thus, liquor samples in such cases should be tested for HMPV too.

Background The treatment of Wilms Tumor is integrated into clinical trials since the 1970's. In contrast to the National Wilms Tumor Study Group (NWTSG) the SIOP trials and studies largely focus on the issue of preoperative therapy to facilitate surgery of a shrunken tumor and to treat metastasis as early as possible. Patients and methods In the SIOP 93-01/GPOH trial and study 1 020 patients with a newly diagnosed renal tumor were registered. 847 of them had a histological proven Wilms Tumor, of whom 637 were unilateral localized, and 173 tumors had an other histology [40 congenital mesoblastic nephroma (CMN), 51 clear cell sarcoma (CCSK), 24 rhabdoid tumor (RTK) and 58 other tumors]. Preoperative chemotherapy in benign tumors was given to 1.3 % of the patients. The main objective of the trial was the randomized question, if the postoperative two drug chemotherapy for stage I in intermediate risk or anaplasia can be reduced from conventional 3 courses to an experimental 1 course without loss of efficacy. Results 519 patients with unilateral nonmetastatic Wilms did receive preoperative chemotherapy. The histology in this group of patients was of intermediate risk in 469 (90 %) patients, 14 (3 %) tumors were low risk and 36 (7 %) high risk. The stage distribution of the tumors was stage I in 315 (61 %), stage II N- in 126 (24 %), stage II N+ in 25 (5 %) and stage III in 36 (7 %) patients. In 17 (3 %) patients the tumor stage remained unclear. Tumor volume was measured in 487 patients before and in 402 after preoperative chemotherapy. The median tumor volume did shrink from 353 to 126 ml. The amount of volume reduction depends on the histological subtype. The event free survival (EFS) after 5 years was 91 % for all patients with unilateral Wilms tumor without distant metastasis. Randomisation was done in 43.7 % for stage I patients and there was no difference in EFS for both treatment arms (90 versus 91 %). The EFS is identical for patients with stage I and II N- (0.92), as well as for stage II N+ and III (0.82). The tumor volume after chemotherapy is a prognostic factor for intermediate risk tumors with the exception of epithelial and stromal predominant tumors. These two subtypes often present as large tumors, they do not shrink during preoperative chemotherapy but they still have an excellent prognosis. On the other hand the prognosis of patients with blastemal predominant subtype after preoperative chemotherapy is worse than in any other patient group of intermediate risk tumors. There are less blastemal predominant tumors compared to primary surgery, but they are chemotherapeutic resistant selected by the preoperative chemotherapy. Conclusion Patients with unilateral Wilms tumor without metastasis have an excellent prognosis. The post-operative chemotherapy in stage I can be reduced to 4 weeks without worsening treatment outcome. The reduction of the tumor volume could be identified as a helpful marker for stratification of post-operative treatment. Post-chemotherapy blastemal predominant subtype of Wilms tumor has to be classified as high risk tumor. Focal anaplasia has a better prognosis than diffuse anaplasia and will be classified as intermediate risk tumor.

19 children and adolescents with intracranial tumors received a palliative therapy with H 15 at a maximum dose of 126 mg/kg BW/day. All patients had previously been treated with conventional therapy. No side effects were observed during a median 9 months application. The recently reported antiedematous effect of H 15 was documented by MRI in one patient with a peritumoral edema, thus sparing steroid therapy with its typical side effects. Five/19 children reported an improvement of their general health status; this might be a psychological effect of hope for tumor response during palliative care. Three/17 patients with malignant tumors showed a mainly transient improvement of neurological symptoms such as pareses and ataxia. Three further patients showed an increased muscular strength and one cachectic patient achieved a weight gain. These improvements might be attributed to the antiedematous effect of H 15. Because of the palliative situation of these patients, H 15 application was performed without prior rebiopsy for histological evaluation. Overlapping effects with a previous radiotherapy or chemotherapy may have occurred. An antiproliferative effect cannot be stated. To prevent an uncritical use of H 15, further studies with prospective central documentation have to be initiated to evaluate the clinical indications for H 15 in palliative therapy, optimal dosage and duration of application.

Intensive chemotherapy has improved the prognosis of patients with AML. The success rate of relapse treatment correlates with the length of first remission. Thus early relapses and primarily refractory diseases have a grave prognosis. New chemotherapeutic regimens could be useful for those patients. Patients treated for newly diagnosed or relapsed AML with polychemotherapy regimen of the AML-BFM-studies containing induction, consolidation and high-dose cytarabine combined with mitoxantrone (HAM) and relapsed within 2 up to 31 months after the first CR entered a pilot trial, the so called IDA-FLAG regimen. This regimen includes G-CSF (day 0 up to ANC > 1000/microliter, 400 micrograms/m2.d), fludarabine (day 1-4, 30 mg/m2.d), high-dose cytarabine (day 1-4, 2000 mg/m2.d) and idarubicin (day 2-4, 12 mg/m2.d). 10 patients aged 1,8 to 28,1 years (mean = 9,6 years) having the first (n = 8) or second relapse (n = 1) of AML or an acute blastcrisis of myelodysplastic syndrome (n = 1) (FAB classification: M1/M2 = 3, M4/M5 = 5, M7 = 1, CMML = 1) received 14 courses. Overall, 7 patients achieved CR with a mean duration of 8,9 months (1-22 months), one patient showed a partial remission and two were nonresponders. 4 patients are in continuous CR for 7,5 to 22 months (mean = 13,2 months). 3 patients got a bone marrow transplantation (allogenic = 2, autologous = 1) in CR following this treatment. Toxicity was considerable, mainly bone marrow aplasia with leucopenia < 1000/microliter for 15 to 40 days (mean = 26,1 days), neutropenia < 500/microliter for 14 to 39 days (mean = 26,0 days) and thrombocytopenia < 30,000/microliter for 14 to 90 days (mean = 36,5 days). Further important side effects were fever, mucositis and pneumonia. One patient died from an fulminant aspergillus sepsis during long-term neutropenia. The sequential administration of G-CSF, fludarabine, cytarabine and idarubicin is effective in treatment of relapsed AML in childhood and an advisable option prior to allogenic or autologous bone marrow transplantation. With regard to the unfavorable prognosis of relapsed or refractory AML the toxicity of this regimen seems acceptable.

Despite its wellknown adverse effects, Amphoterin B is an integral part of any supportive therapy in haematology/oncology. We report on a thirteen year old boy with acute myelogenous leukemia and suspected fungoid pneumonia. Shortly after iv or inhalative application of Amphotericin B he repeatedly presented with a Raynaud phenomenon of his toes, which ceased after switching to Ambisome (liposomal unilamellar encapsuled Amphotericin B). Since there is evidence that thromboxane A2-mediated arteriolar spasms of renal vessels provoke the wellknown increase in serum creatinine after Amphotericin B, and in different species pulmonal vasoconstriction has been observed, we speculate that a similar mechanism is responsible for the observed Raynaud phenomenon. Thus we suggest inhibitors of prostaglandine synthesis for therapy.

Owing to the unclear and mostly unknown etiology of Langerhans' cell Histiocytosis (LCH) and the unsatisfactory results in treating disseminated LCH a prospective multicentric study DAL-HX 83 was commenced, including 45 different clinics of West-Germany, Austria and Netherlands. From June 1st, 1983 to October 31st, 1986, 97 patients (pts) were involved in this study. 35 pts (9 females, 26 males, medium age 6 2/12 years, age range 0/12-14 2/12 years) suffering from localized disease (28x unifocal bone, 6x isolated skin, 1x isolated lymphnode involvement) were treated by surgery and/or radiation or were just kept in observation. 2 children (1 pt with primary localized bone lesion, 1 child with isolated skin rash) developed a new bone lesion after 1/2 year and 1 1/2 years respectively. 62 pts (33 females, 29 males, medium age 2 years, range 0/12-17 1/2 years) with previously untreated disseminated disease were assigned to 3 different risk groups (A, B and C) and were treated according to a standardized induction and risk adapted maintenance protocol. The whole treatment period was limited to 1 year. 19 pts with multifocal bone involvement (group A, medium age 6 1/2 years) were allocated to regimen A, 30 pts with bone and soft tissue involvement or soft tissue involvement alone (group B, medium age 1 8/12 years) to regimen B and 13 pts with dysfunction of the liver, lungs and/or haematopoietic system (group C, medium age 1 year) to regimen C. So far, 1 pt of group A (19 available pts) developed a new bone lesion after 10 months, another pt a suspicious bone involvement 16 months after diagnosis. A 4 months old girl of group B (27 available pts) died 11 months after diagnosis with progressive organ dysfunction, 2 pts are still alive with recurrent multifocal bone lesions and 1 pt achieved stable 2nd clinical remission after a local relapse (mediastinum). 4 pts of group C (11 available pts) died because of progressive disease between 5 days and 3 years after diagnosis, 3 pts are in partial remission after persistent and recurrent disease episodes. All the others are in clinical remission. The medium observation time of the whole group of pts with disseminated LCH is 1 9/12 years (range 0/12-3 5/12 years). The worst prognostic criteria were found to be the presence of organ dysfunction at diagnosis or its development during the course of disease and the age under two years.(ABSTRACT TRUNCATED AT 400 WORDS)

Eleven young patients with relapsed childhood malignancies received continuous infusions of 5-10 mg/m2/day doxorubicin. 30 infusions were given via a central venous access until signs of mucositis showed up (7-52 days). Other toxicity was low, both bone marrow depression and fever and neutropenia occurred in 7/30 and 5/30 courses of therapy, respectively. No signs of liver or cardiac toxicity were seen in these heavily pretreated patients. In 8/11 patients tumor regression was documented, though only two partial remission were noted. Continuous infusions of doxorubicin are an effective and relatively non-toxic treatment for relapsed childhood malignancies. Since this form of therapy enables good quality of life and medical care on ambulatory basis, a phase II-study of low-dose doxorubicin for relapsed tumors is justified.